Filgrastim prevents severe neutropenia and reduces infective morbidity in patients with advanced HIV infection: results of a randomized, multicenter, controlled trial. G-CSF 930101 Study Group.
OBJECTIVE
To assess the effect of filgrastim treatment on the incidence of severe neutropenia in patients with advanced HIV infection, and the effect of initial filgrastim treatment on prevention of infectious morbidity.


METHODS
Randomized, controlled, open-label, multicenter study.


METHODS
Outpatient centers and physician offices.


METHODS
Men and women aged > 13 years, who were HIV antibody-positive, and had a CD4 cell count < 200 x 10(6)/l, absolute neutrophil count (ANC) 0.75-1.0 x 10(9)/l, and platelet count > or = 50 x 10(9)/l within 7 days of randomization were eligible. Two hundred and fifty-eight patients entered and 201 completed the study.


METHODS
Daily filgrastim (starting at 1 microg/kg daily, adjusted up to 10 microg/kg daily) or intermittent filgrastim (starting at 300 microg daily one to three times per week to a maximum of 600 microg daily 7 days weekly) was administered to maintain an ANC between 2 and 10 x 10(9)/l. Patients in the control group received filgrastim if severe neutropenia developed.


METHODS
Incidence of severe neutropenia (ANC < 0.5 x 10(9)/l) or death, incidence of bacterial and fungal infections, duration of hospitalization and intravenous antibacterial use, and safety.


RESULTS
The primary endpoint of severe neutropenia or death was less frequent in patients who received daily (12.8%) or intermittent (8.2%) filgrastim compared with control patients (34.1%; P<0.002 and P<0.0001 for comparison with daily and intermittent groups, respectively). Filgrastim-treated patients developed 31% fewer bacterial infections and 54% fewer severe bacterial infections than control patients, required 26% less hospital days including 45% fewer hospital days for bacterial infections, and needed 28% fewer days of intravenous antibacterials. Filgrastim was not associated with an increase in HIV-1 plasma RNA level in a subset of patients in whom this was measured or any new or unexpected adverse events.


CONCLUSIONS
Filgrastim was safe and effective in preventing severe neutropenia in patients with advanced HIV infection, and may reduce the incidence and duration of bacterial infections, incidence of severe bacterial infections, duration of hospital days for infections, and days of intravenous antibacterial agents.
Kuritzkes
D R
DR
University of Colorado Health Sciences Center, Denver 80262, USA.
Parenti
D
D
Ward
D J
DJ
Rachlis
A
A
Wong
R J
RJ
Mallon
K P
KP
Rich
W J
WJ
Jacobson
M A
MA
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001424:Bacterial Infections / Q000175:diagnosis / Q000188:drug therapy; D018791:CD4 Lymphocyte Count; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006678:HIV / Q000302:isolation & purification; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000175:diagnosis / Q000188:drug therapy; D009503:Neutropenia / Q000517:prevention & control*; D010045:Outpatients; D010976:Platelet Count; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D012367:RNA, Viral; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim